Identification

Name
UC-781
Accession Number
DB05871  (DB08679)
Type
Small Molecule
Groups
Investigational
Description

UC-781 is a thiocarboxanilide non-nucleoside reverse transcriptase inhibitor (NNRTI). It is a topical microbicide targeted against the AIDS virus.

Structure
Thumb
Synonyms
Not Available
External IDs
NSC-675186 / UC781
Categories
UNII
L7K247H29H
CAS number
178870-32-1
Weight
Average: 335.848
Monoisotopic: 335.074677222
Chemical Formula
C17H18ClNO2S
InChI Key
YZHIXLCGPOTQNB-UHFFFAOYSA-N
InChI
InChI=1S/C17H18ClNO2S/c1-11(2)6-8-21-16-10-13(4-5-15(16)18)19-17(22)14-7-9-20-12(14)3/h4-7,9-10H,8H2,1-3H3,(H,19,22)
IUPAC Name
N-{4-chloro-3-[(3-methylbut-2-en-1-yl)oxy]phenyl}-2-methylfuran-3-carbothioamide
SMILES
CC(C)=CCOC1=C(Cl)C=CC(NC(=S)C2=C(C)OC=C2)=C1

Pharmacology

Indication

Investigated for use/treatment in HIV infection.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

UC-781 is an HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) that has shown in vitro to be very active specifically against HIV-1. UC-781 exhibits synergy with the NRTI zidovudine in vitro.[12] The combination of UC-781 and another candidate microbicide, cellulose acetate 1,2-benzenedicarboxylate, resulted in effective synergy for inhibition of HIV-1 in vitro and in peripheral blood mononuclear cells

TargetActionsOrganism
UGag-Pol polyproteinNot AvailableHIV-1
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Patton DL, Sweeney YT, Balkus JE, Rohan LC, Moncla BJ, Parniak MA, Hillier SL: Preclinical safety assessments of UC781 anti-human immunodeficiency virus topical microbicide formulations. Antimicrob Agents Chemother. 2007 May;51(5):1608-15. Epub 2007 Mar 12. [PubMed:17353240]
  2. Hossain MM, Parniak MA: In vitro microbicidal activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) UC781 against NNRTI-resistant human immunodeficiency virus type 1. J Virol. 2006 May;80(9):4440-6. [PubMed:16611904]
External Links
PubChem Compound
3000926
PubChem Substance
175427049
ChemSpider
2272425
BindingDB
50105629
ChEMBL
CHEMBL54893
HET
UC1
PDB Entries
1jlg / 1rt4 / 1s1t / 1s1w

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0123 mg/mLALOGPS
logP4.07ALOGPS
logP5.1ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)10.85ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area34.4 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity97.63 m3·mol-1ChemAxon
Polarizability35.48 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9944
Blood Brain Barrier+0.868
Caco-2 permeable+0.5624
P-glycoprotein substrateNon-substrate0.7838
P-glycoprotein inhibitor IInhibitor0.7317
P-glycoprotein inhibitor IINon-inhibitor0.7672
Renal organic cation transporterNon-inhibitor0.7839
CYP450 2C9 substrateNon-substrate0.7202
CYP450 2D6 substrateNon-substrate0.7351
CYP450 3A4 substrateSubstrate0.5916
CYP450 1A2 substrateInhibitor0.8428
CYP450 2C9 inhibitorInhibitor0.7788
CYP450 2D6 inhibitorNon-inhibitor0.7976
CYP450 2C19 inhibitorInhibitor0.8637
CYP450 3A4 inhibitorInhibitor0.6668
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.97
Ames testNon AMES toxic0.5371
CarcinogenicityNon-carcinogens0.7322
BiodegradationNot ready biodegradable0.9941
Rat acute toxicity2.5074 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7043
hERG inhibition (predictor II)Non-inhibitor0.7358
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Not Available
Direct Parent
Phenol ethers
Alternative Parents
Phenoxy compounds / Chlorobenzenes / Alkyl aryl ethers / Aryl chlorides / Thioamides / Heteroaromatic compounds / Furans / Thiocarboxylic acid amides / Oxacyclic compounds / Thiocarbonyl compounds
show 4 more
Substituents
Phenoxy compound / Phenol ether / Alkyl aryl ether / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Heteroaromatic compound / Furan
show 16 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
HIV-1
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Gag-Pol polyprotein: Mediates, with Gag polyrotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spher...
Gene Name
gag-pol
Uniprot ID
P03366
Uniprot Name
Gag-Pol polyprotein
Molecular Weight
163287.51 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on November 18, 2007 11:28 / Updated on December 01, 2017 15:37